DESCRIPTION (Investigator's Abstract): Stroke is a major cause of death and disability in the USA. Promising pharmacological strategies aimed at reducing clinical severity of stroke outcome in patients have followed from elucidation of the molecular mechanisms of ischemic neuronal injury in animal models. Identification of human stroke victims for intervention and evaluation of treatment efficacy in patients has depended primarily on clinical assessments rather than physiological measurements, since the capacity to rapidly study ischemic pathophysiology in humans is limited. New, ultrafast magnetic resonance imaging (MRI) methods open up the possibility to non-invasively study aspects of human ischemic pathophysiology. These innovations include echo planar imaging (EPI), a class of MRI pulse sequences that permits imaging on the order on 100 ms, diffusion weighted imaging (DWI), which is sensitive to decreases of water self-diffusion within minutes after ischemia onset and a marker for cellular energy failure, and MR perfusion imaging. Two aspects of perfusion studied with MR include dynamic blood volume imaging and relative cerebral blood flow mapping with EPISTAR, a new technique recently developed and validated by our group. We have made rapid diffusion and perfusion measurements in acute stroke patients and followed changes in these parameters over time. We have operationally defined and preliminarily identified the ischemic penumbra as a region, destined for infarction, of acutely reduced perfusion surrounding the core of energy failure (decreased diffusion). The project aims are: 1. To validate the methodologies for EPI diffusion and perfusion weighted acquisitions and volumetric measurements of ischemic lesions. 2. To determine the temporal evolution of lesion volume: when does the lesion reach its final size? 3. To determine the depth of reduction in relative cerebral blood volume and relative cerebral blood flow that predicts progression to infarction. These aims will be accomplished by serial multislice EPI diffusion and perfusion measurements of stroke patients at two time points, acute and chronic. The variables measured will be the apparent diffusion coefficients, relative blood volumes and relative blood flows. Volumes of lesions will also be measured. Clinical evaluations using the NIH Stroke Scale will be compared to the MR measurements. The overall goal of this research is to better understand the pathophysiology of human ischemic stroke and to provide objective criteria beyond the clinical exam by which it can be evaluated. It is only against the background of quantifiable physiological measurements that potential stroke therapies, such as neuroprotective drugs, can be accurately assessed and rational predictions about their appropriate use be made.